Good morning and welcome, ladies and gentlemen, to Cytokinetics conference call. At this time, I would like to inform you that this call is being recorded and that all participants are in a listen-only mode. At the company's request, we will open the call for questions and answers after the presentation. I will now turn the call over to Diane Weiser, Cytokinetics Vice President of Corporate Communications and Investor Relations. Please go ahead.
Good morning. Thank you for joining us on the call today. Robert Blum, our President and Chief Executive Officer, will lead with an overview of Saturday's announcement. Fady Malik, our Executive Vice President of Research and Development, will provide a brief background on reldesemtiv and our phase I data before Dr. John Day recaps key findings from the recently presented phase II study of reldesemtiv in patients with SMA. Robert will provide some closing remarks before we open the call to questions. Andy Wolff, our Chief Medical Officer, and Ching Jaw, our Chief Financial Officer, are also with us on the call to participate in the Q&A. Portions of the following discussion, including our responses to questions, contain statements that relate to future events and performance rather than historical facts and constitute forward-looking statements for purposes of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995.
Examples of forward-looking statements may include statements relating to the potential benefits of reldesemtiv in patients with SMA, our strategic initiatives, our collaboration with Astellas, clinical trials, and the potential for eventual regulatory approval of our product candidates, including reldesemtiv. Our actual results might differ materially from those projected in these forward-looking statements. Additional information concerning factors that could cause our actual results to differ materially from those in these forward-looking statements is contained in our SEC filings, including our most recent 10-K, 10-Q, and 8-Ks. We undertake no obligation to update any forward-looking statements after this call. Now I will turn the call over to Robert.
Thank you, Diane. Thanks again to everyone for joining us on the call today. This past Saturday, June 16, Cytokinetics announced that data from the phase II clinical study of reldesemtiv in patients with spinal muscular atrophy, or SMA, were presented by Dr. John Day, Professor of Neurology and Pediatrics at Stanford University, at the 2018 Annual SMA Conference in Dallas. We are very pleased to have Dr. Day on the call with us this morning. Thank you, John, for joining us. As our press release stated, we believe that this hypothesis-generating study met its primary objective to determine potential pharmacodynamic effects of reldesemtiv after multiple oral doses in patients with SMA, as well as secondary objectives to evaluate the safety, tolerability, and pharmacokinetics of reldesemtiv.
As you know, we're developing reldesemtiv in collaboration with Astellas as a potential treatment for people with SMA, as well as certain other diseases and conditions associated with skeletal muscle weakness and/or fatigue. As John will elaborate, the study showed dose and concentration-dependent increases in time to muscle fatigue as measured by changes from baseline in six-minute walk distance, a submaximal exercise test of aerobic capacity and endurance, and maximal expiratory pressure, or MEP, a measure of strength of respiratory muscles, in both cases after eight weeks of treatment with reldesemtiv. As some of you know, the Cure SMA meeting is a special meeting providing a rare opportunity for researchers and industry to meet directly with patients and loved ones courageously living with SMA and to share updates on clinical progress.
We were pleased to share the results of this study with the SMA community, as we believe this study provides the first data indicating that a muscle-directed therapy, namely a fast skeletal muscle troponin activator or FASTA, may hold promise for potential clinical benefit for patients with SMA. With that, I'll turn it over to Fady to remind you of the mechanism of reldesemtiv and recap some key findings from the phase I clinical trials program that informed the design of our study in SMA.
Thanks, Robert. Reldesemtiv is a next-generation fast skeletal muscle troponin activator or FASTA. As you'll recall, it has the same mechanism as tirasemtiv but was selected and optimized from a different and distinct chemical series. As we found in our phase I clinical trials program, reldesemtiv may have a more favorable tolerability profile relative to tirasemtiv with regard to lightheadedness and other potential adverse effects. The most telling phase I study looked at the pharmacodynamic effects in healthy volunteers and was similar to a previous study conducted with tirasemtiv. In this study, we stimulated the deep fibular nerve, which runs on the outside of the knee and controls the tibialis anterior muscle in the front of the leg. The force produced during stimulation of the nerve was measured before and at several points after single doses of reldesemtiv were administered to healthy subjects.
We found the magnitude of response was twice as large over a range of plasma concentrations that was approximately half that which we observed with tirasemtiv. This is largely because reldesemtiv is less protein-bound and therefore penetrates muscle more effectively, producing a larger effect. Additionally, the tolerability issues observed with tirasemtiv in phase I were not observed with reldesemtiv. Based on the results presented this weekend, it seems the tolerability and side effect profile of reldesemtiv, as well as its impact on muscle force, power, and stamina, may be translating to patients with SMA, as evidenced by the improvements observed in six-minute walk distance and maximal expiratory pressure. Now, I'll turn it over to Dr. Day to review the key findings from the phase II study. Before that, I'll review a couple of key slides with regards to the mechanism of actions and the phase I data.
Turning to the slide deck, on slide two, just to remind you, reldesemtiv is a selective small molecule activator of the troponin complex in skeletal muscle. It increases the affinity of the troponin complex for calcium and thus sensitizes the sarcomere to calcium and nerve input, which causes the release of calcium inside of muscle to activate muscle. The next slide shows some preclinical work that was done in two models of spinal muscular atrophy. The one on the left is a more severe model. You can see that stimulating the nerve to the leg muscles there results in a certain amount of force in the control animals on the left in the gray bar. In the blue bar, these animals are much weaker, with only about 20% of the force of their controls being produced by the same nerve stimulation.
Administration of reldesemtiv at two doses increases the amount of force produced in the green bars. On the right, it shows a less severe model of SMA, again, with somewhat reduced force at baseline. Here, reldesemtiv producing greater forces at the same nerve stimulation rate as was done in the control and vehicle-treated animals. The next slide shows translation of this mechanism of action into humans in a similar experiment in which reldesemtiv was administered to healthy volunteers in three doses, and also placebo was given. The doses were administered in a random fashion and also blinded, of course, to both the investigator and the subjects. The fibular nerve there was stimulated, eliciting an increase in force dorsiflexion of the foot. Again, what you see here are concentration-dependent increases in force subsequent to the dosing of reldesemtiv.
The doses that we studied in CY5021 were expected to produce plasma concentrations in the lower and higher range of pharmacodynamic effects observed in this slide which is important as we go on, as Dr. Day will point out. With this translation of mechanism into humans, we embarked on conducting study CY5021 in patients with SMA. Now I'll turn it over to Dr. Day, who will present the study results.
Great. Thanks, Fady. We're up to slide five, and basically, this is a hypothesis-generating study that we devised to investigate the effects of reldesemtiv in SMA. Slide six sketches out a little bit more about this study that was really designed to study the pharmacokinetic and pharmacodynamic and safety features in two cohorts dosed at 150 and 450 milligrams twice daily. Importantly, in the inclusion and exclusion criteria, we were studying an older age group than is studied in most SMA studies looking at types 2, 3, and 4, and used the Hammersmith functional motor score to identify the appropriate population, excluding patients that were either too weak and had a Hammersmith less than 10 or too strong and had a Hammersmith greater than 54. That will come back in terms of the population that we studied as evidenced on the next slides.
This just shows the construct of the study again, where we had two cohorts, the low dose and the high dose, trying to maintain equal numbers of ambulatory and non-ambulatory patients, then randomizing at a 2-to-1 treated-to-placebo ratio for those groups. The subsequent slide eight shows the intensity of this study. It was at most 15 weeks, but during that time, the patients had seven study visits so that we followed them quite closely. It should be pointed out that the final data lock will actually be later this week as we collect the last data on the follow-up visits. On slide nine, you can see the outcome measures that we used. Again, pointing out the various measures that we followed during this. The one point here is that the SMA Health Index was only available to us for Cohort 2.
That was not yet available for us for the low-dose cohort. Then in terms of the actual patients that we enrolled, you can see that we enrolled on the left, 39 subjects in Cohort 1, and on the right, 31 in Cohort 2. We maintained a fairly good balance between ambulatory in green and non-ambulatory in blue. As evidenced on the slide in Cohort 1, we had two early terminations, but both were from the placebo arm of that cohort due to Adverse Events that occurred in those subjects. In Cohort 2, we had three early terminations, one due to a protocol deviation, and one because they withdrew for another study. One due to an Adverse Event, as we'll discuss. In terms of the demographics, there were no significant differences between the three groups of placebo, low-dose, and high-dose cohorts.
You will note that most of the patients ended up being of Type 3, even though Type 2, 3, and 4 were opened for enrollment. Type 2 patients by and large were too weak and had Hammersmith below 10, and Type 4 patients were all too strong, having Hammersmiths greater than 54. In the next slide, you can see the baseline characteristics, and again, there is no significant difference between the groups in these measures going into the trial. Again, pointing out that the SMA Health Index was not available to us for that low-dose cohort. Slide 13, I think we're up to, shows a forest plot of a lot of the results. You can see that many of the studied parameters did not change. On the left, you can see the low-dose cohort, and on the right, the high-dose cohort.
Points that tend to favor placebo edge to the left of the median line and towards reldesemtiv to the right. Two particular parameters stand out, namely the maximum expiratory pressure, MEP, and the six-minute walk distance. You can see in this overall graph of all participants, there does seem to be a dose-dependent increase in effect in those two parameters for both maximum expiratory pressure and six-minute walk distance. We pulled out the six-minute walk distance to look at a little bit more closely, and this shows the effect over time for that measure in the gray line showing the placebo group, the light green, the low-dose cohort, and the dark green, the high-dose cohort, showing again, evidence of a fairly clear dose response improvement in the six-minute walk distance.
The waterfall plot reiterates that point, again showing several individuals having a significant improvement on the high dose, a tendency for the placebo patients to have little effect or deteriorate, and the lower dose cohort to be in the middle. Graphing this out versus the drug exposure on the X-axis there in Slide 16, you can see the peak of plasma concentration measured during pharmacokinetic studies on the same day as these six-minute walk distances were measured, showing a fairly significant dose relationship between the increase in six-minute walk distance with a P value for this of less than 0.01. I should go back to that slide. If you could take me back, Diane. On Slide 16, you can see that even the highest concentration there was less than five.
If we look at the quartiles of the highest dose quartile was significantly less than the target of six or seven micrograms per milliliter. On the next slide, you can see again what Fady had pointed out in terms of the study of control subjects earlier. Our target range for the high dose was in the upper end of that dose response curve, and we did not achieve that, which we assume is due to a change in drug formulation. You can see the graded box there showing the hoped-for range of exposure and the green box at three to four micrograms per milliliter shows the concentration actually achieved in the top quartile of the patients in 5021. In terms of side effects, there were no significant AEs that differentiated between the placebo, low dose, and high dose subjects.
The most common Adverse Events were headache and gastrointestinal issues, those were fairly similar between the different cohorts, no other significant toxicity was identified. In terms of serious AEs, there were four subjects that experienced serious AEs, none of which were thought to be related to drug. Three of them had clearly superimposed problems, the salmonella, facial pain, and a fall and a fracture. The fourth subject had elevated serum creatine phosphokinase that was attributed to his, at the end of the treatment period, becoming overly active and undertaking a significant home improvement episode, and apparently had a transient CK elevation at that time. It did not affect his treatment with the drug and resolved spontaneously.
In conclusion, we think that this hypothesis-generating study is seeming to show some indication of muscle-directed improvement relevant to the SMA population, namely in terms of six-minute walk distance and maximum expiratory pressure. We note that there was no efficacy plateau demonstrated, we think that there is a likelihood that increasing the drug exposure can further amplify this response. We believe that the lower than expected drug exposure is attributed to a change in drug formulation that can be rectified with increased dosing. There were no safety or tolerability issues that would prevent us from doing that. In essence, I think that the study did its job in generating some valid hypotheses that can be explored further with this compound. Thank you very much for the opportunity to go over this with you.
Thank you, John. These are very exciting times and optimistic times for the SMA community. The future for patients living with SMA today is brighter than ever with the recent introduction of gene-directed therapies. Today, it's expected that patients may live longer with the advent of new therapies, but still have a significant unmet need. Sorry. Today, it's expected that patients may live longer with the advent of new therapies, but we'll still have a significant unmet need with expected disabilities related to respiration and mobility. We estimate approximately 50% of Type 3 patients with SMA are believed to maintain ambulatory function today, and an increasing number of Type 2 patients with SMA are expected to remain ambulatory with the advent of complementary new therapies that can enable motor milestones.
Over the next five years, the prevalence of ambulatory adolescents and adults with SMA may exceed 5,000-10,000 patients in the United States alone. While we did not see effects on all of the assessments explored in this phase II hypothesis-generating study, that was to be expected, and we're encouraged to see that treatment with reldesemtiv produced dose and concentration-dependent clinically meaningful benefits in six-minute walk distance, as well as maximal expiratory pressure. With these data in hand, together with our partner Astellas, we'll be evaluating potential next steps in the development plan for reldesemtiv. Once we've completed a full analysis of the clinical study data, we'll seek guidance from the SMA community, clinical experts in SMA, and regulatory authorities as may inform a potential path forward for this drug candidate.
We look forward to continuing our analyses and charting a path forward for reldesemtiv as we await results from the additional trials in COPD, ALS, and elderly subjects with limited mobility, all part of our broad mid-stage development program in collaboration with Astellas. We remain optimistic about the promise and potential of this drug candidate, and we look forward to keeping our partners in the disease communities and our shareholders apprised of our progress. Operator, with that, we can now open up the call to questions, please.
Ladies and gentlemen, at this time, if you would like to ask a question, please press star one on your telephone keypad. Again, to ask a question, please press star, then the number one. We will pause for just a moment to compile the Q&A roster. Your first question comes from the line of Matthew Harrison with Morgan Stanley.
Good morning, Matthew.
Great. Good morning. Thanks for taking the questions. I think two for me, if possible. The first one, maybe for Dr. Day. Maybe you could just comment a little bit on where you might-- If this therapy can demonstrate a benefit in six-minute walk, where would you think this will fit in the treatment paradigm given what we've seen from some of the other agents on the market? A second one for the company. Maybe you could just also remind us, given the dose exposure levels that you've seen, what that means for some of the other studies that you're running with reldesemtiv. Thanks.
Excellent. John, maybe I'll defer to you for the first question, and Fady, to you for the second.
Sounds good. Sure. As you may be aware, in SMA, we've long been seeking somewhat symptomatic treatments as well as these disease-modifying treatments.
That you allude to that are now being increasingly made available. I think that this can function as a very significant add-on to those treatments. The hope is that patients will improve with the SMN protein modifying treatments, very, very few of those patients are actually normal. Almost all of them have residual motor deficits. I think that coming up with a mechanism to improve their efficiency of force generation will definitely be something that will have a place in the entire SMA community.
I'll take the same part of the question. As we mentioned, we think we have room to move higher in this study, the range of exposures that we achieved are still quite substantially pharmacodynamically active and more so when compared to tirasemtiv, which we studied in ALS. We think the ALS study is doses that we've selected and exposures that we'll observe are sufficient for us to confirm the hypothesis that we laid out in that study, which is that reldesemtiv will slow the decline in slow vital capacity as we observed with tirasemtiv.
Great. Thanks very much.
Thank you, Matthew.
Your next question is from the line of Chad Messer with Needham.
Good morning, Chad.
Good morning. Thanks for taking my question, congrats on the encouraging data, particularly with regards to safety tolerability and six-minute walk. Given that this was a hypothesis-generating study, I wonder if you guys have any mechanistic hypotheses as to why we're seeing this effect on maximal expiratory pressure in the non-ambulatory patients, not in the ambulatory ones, no effect on SVC, perhaps some difference to the two diseases. Just wanted to get your thoughts on that.
Sure. I'll start, I'll ask Fady to speak about what we know regarding maximal expiratory pressure or MEP, what that's measuring, why that may translate to the properties of reldesemtiv, maybe ask Andy also to step in and remind everyone on the call about some of the data we had generated early on with tirasemtiv in terms of this mechanism and extending time to muscle fatigue across a broad array of other populations with muscle weakness. Fady, do you want to start?
I think we observed improvements in MEP in both populations. The effects were greater in the non-ambulatory population, and the baseline data in those groups was substantially lower. They had lower MEPs at baseline and thus had more headroom to improve. The maximum expiratory pressure is a maneuver that requires the diaphragm, the abdominal muscles, the chest wall muscles. It's a somewhat sustained effort over a few seconds that is potentially correlated with patient's ability to cough and other things. We think of it as a measure of muscle function that is confirmatory.
The effects on forced vital capacity we didn't see, the baseline forced vital capacity in these patients is close to normal, about 85% of predicted, although you have to recognize that predicted is based on healthy volunteers with normal body habitus and normal thoraces and so forth, which these patients often don't have given their scoliosis and other skeletal muscle or skeletal deformities. I think it's a confirmatory signal. The six-minute walk distance is a much different kind of metric that looks more at fatigability with repetitive movements over six minutes. Maybe I'll turn it over to Andy, who can talk about some of our development experience with tirasemtiv in that regard.
Potentially, I think what Robert was referring to is why six-minute walk among some of the other tests. One thing that can improve six-minute walk distance is diminished fatigability. It's obviously something that occurs over an extended period of time. With tirasemtiv, our first fast skeletal muscle troponin activator, you may recall that we did a study in myasthenia gravis where we saw significant improvements in the QMG score. When you look at those data, some of the most prominently affected components of that score were those that were related to endurance and not maximal effort. How long a person could hold their head up off of a supine position, for example, or hold their arm out from their body.
We also did a similar earlier study with tirasemtiv in patients with claudication in their calf muscle, where we asked them to do heel lifts, where they went up on their toes as high as they could and came back down. They did that every other second. There was a metronome. We could measure the angle of the elevation, and we weighed them as well, so we could calculate the actual work that that claudicating muscle did before it finally fatigued.
We saw that with tirasemtiv, patients did significantly more work. They went higher for a longer period of time before they finally did have to stop because of either intolerable pain or just inability to do it. There's a prominent anti-fatigability effect of the drug, and we knew that from preclinical data as well.
Okay, great. Thanks. That's all actually very helpful and makes sense. Maybe just one more on formulation. It sounds like you guys were kind of surprised or mispredicted what kind of exposure you would get with this formulation. Where are you in terms of finalizing formulations? Is there more work you need to do here, or are you fairly confident that you'll have enough data to basically design future studies?
Sure. I'll mention a couple things already, and then maybe Fady can elaborate if necessary. The formulation development work is a continuing process that has already been underway with our colleagues at Astellas. There are new process development and new formulation sciences activities that got started well before we had these data in anticipation of taking forms into pivotal studies that would address not only some of the issues that you've heard about, but also help to ensure that we have better cost of goods and other efficiencies and optimized processes for what could ultimately be commercial scale manufacturing. It's a continuum, and we're already deep into those activities.
All right, great.
Yeah. I'll just maybe expand in that. The increase between 150 and 450 milligrams twice a day in the study was linear. We got about threefold the exposure for threefold the dose. We've seen that at higher doses as well in healthy volunteers. One approach is simply to increase the dose, and we would expect to see an exposure increase. At the same time, we'll conduct in parallel formulation development activities, to try and optimize exposure of reldesemtiv.
Okay, thanks. Look forward to hearing a lot more about reldesemtiv in the future.
Thank you, Chad.
Your next question is from the line of Joe Padgett with H.C. Wainwright.
Good morning, Joe.
Hey, guys. Good morning. Good morning. Thanks for taking the question. First question, maybe for Dr. Day. With the premise that these data have very limited comparators with SPINRAZA or nusinersen being the only drug on the market, can you talk to the appropriateness even of using the Hammersmith scale in this population? Because nothing was seen in this study for Hammersmith, whereas it's in the label based on Study 2 for SPINRAZA. Again, can you just discuss even the appropriateness of using Hammersmith for this population? Thanks.
Yeah, John, I'll turn that to you.
Okay. I think several points. I mean, the Hammersmith was really devised for infants and young children. Consequently, using it for this population is questionable to start with. We used it because of the familiarity of the therapists with it, and because we did think it would stratify the population well. In terms of an outcome measure going forward, I think it probably will prove itself to be not as effective as something that measures more stamina than just simply power production. Which in essence, is what the Hammersmith is doing.
That's very helpful. Thank you. With regard to the six-minute walk distance, I just had a quick question with regard to the placebo responses. Is this considered in, I guess, any regard to, say, a training effect in these patients, or do you consider it just noise?
John?
In placebos? There's a lot of randomness inevitably in doing the six-minute walk test. I think that that's always a factor when we do this. I think in this instance, we did see an increase of, at different points, tens of meters in different subgroup analyses, upwards of 60 meters in some groups. That's beyond the noise level when we're looking at it that way. I think it's very hard to look at the six-minute walk distance in individuals. In group data like this, that degree of difference is greater than expected. We usually use a cutoff of 30 meters as being more than we would expect to see in group data, and we were getting beyond that in some of the group analyses.
Great. Thank you very much.
Thank you, Joe.
Your next question is from the line of Mara Goldstein with Cantor Fitzgerald.
Good morning, Maura.
Good morning. Just a question. The six-minute walk test and MEP were positive parameters, while mostly others were largely unchanged, with the exception of the muscle mega score, which had a very distinctly different, if you will, I certainly don't want to say pattern, because I understand it's a small trial. It did favor placebo in the ambulatory high dose. Maybe can you just provide some rationale for why the figures are appearing for this particular test parameter?
Well, that's a very good question, and I think while I'll suggest maybe we're seeing a trend, I wouldn't suggest that there was a meaningful finding there. Certainly, it's left leaning towards favoring placebo, but not otherwise deemed statistically significant. Fady and Andy may have explanations they can share.
Thank you.
Yeah, I think there are two things to consider. One is when we looked at the individual data there were a couple placebo patients whose strength improved rather remarkably over the course of the study. That is as measured, I say, because this measurement is dependent both on the patient and the evaluator conducting this. Sometimes, the evaluators in this area where muscle mega score is not used in spinal muscular atrophy, or it's not used regularly. I think potentially we had some evaluators across sites that were not as experienced as other evaluators. It's used more frequently in ALS, and centers are, I think, more used to using it there, and we try to employ it here in SMA to see how it would work.
John can comment on how often placebo patients strength improves by that degree that we observed in some of the individuals.
Yeah, it's again, quite variable and depends a lot on the technique of the investigator as well as various motivational issues that can creep in if somebody isn't feeling well or is exhausted or whatever. I think that we have to look at those individuals a little bit more closely and see if their initial values were low or if their subsequent values were high or whatever. I don't put a lot of stock in it because of that. Again, for the most part, this is more of a measure of muscle force than of stamina. I think that we need to look and see whether or not that is something that we want to even consider going forward.
Okay. If I could also just ask Dr. Day, from a practical perspective, when you think about the idea around either combination or treatment with reldesemtiv and other agents like SPINRAZA, at this point, I understand it's early on, but how would you potentially think that reldesemtiv would be incorporated into a sort of SPINRAZA treated world?
Yeah, I think that's a great question. I think it's illustrative perhaps to look at the AveXis experience, where a significant number, I keep hearing various numbers of patients treated with AveXis have then subsequently been treated with SPINRAZA. I think what that's saying is that there is a residual deficit there. That the motor improvement is not absolute, and consequently, these patients have residual need. My guess is that you're going to max out in terms of the effects of SMN protein upregulation, and it's not a matter of just continuing to increase that you need something beyond SMN protein upregulation. I think there's already a significant need there in terms of developing muscle-directed therapies that are going to augment the effects of these SMN protein regulators. I think it will have a place.
I think it will be very clear in patients that there is value of this type of treatment on top of the SMN protein upregulation approach.
Okay. Thank you.
Your final question is from the line of Vernon Bernardino with Seaport Global.
Good morning, Vernon.
Hi there. Good morning, and congrats again on the results. Thanks for taking my question. Two questions. If you look back on slide 16 and the results on six-minute walk distance. There's great variability, obviously it's not a very large study in the results. Perhaps, Dr. Day, as far as you've seen, over time, at least with the placebo results, do you expect that the performance of these patients perhaps get tighter over time beyond week eight? I guess for Robert and the team, do you expect with a larger study and then higher doses that you'd see tighter results and continued improvement in walking distance?
John, we'll start with you.
Again, looking at individual data in six-minute walk distance is always noisier than looking at group data. Very few people report data on individual subjects just for that reason. We always look at group data for this. I do expect that there will always be some degree of noise, but I do think that the divergence would become more clear with larger N here, that there's going to be a significant difference that will be evident. I think already the p-values are fairly significant for even this small group, so I'm fairly optimistic that we'll see it more clearly in the larger group.
And-
Just to elaborate, if I may. We've consistently seen with this mechanism of fast skeletal troponin activators, dose-dependent and exposure-driven increases in muscle force, muscle power, and time to muscle fatigue. Therefore, we don't expect that there's a difference in this study between what was observed at week four and what was observed at week eight in term of magnitude of effect for any of the dose levels. What will be interesting to see is in future studies, as we may be able to now achieve higher exposures, whether we see, and I expect we may, significantly increased effects with increasing exposures and whether that may translate to cumulative effects over time or just maintained effect consistent with exposure. I think that'll be a key question that we'll want to investigate with potentially further studies. You had another question?
Yes. Thank you. Second question. Dr. Day, in any of the other outcome measures, were there ones would you have liked to have seen positive results or at least significantly positive trends?
This really was, for me, a hypothesis-generating study, so that I didn't start out with any significant preconceived notions about where we were going to see the effects. I think it makes sense that we're seeing it in a six-minute walk distance. I think that the expiratory pressure also makes some sense. That's a very complex move that's utilizing a group of muscles, some of which are more and less affected in SMA. I think that's intriguing and one that we're going to want to dive into a little more. The other outcome measure I'm interested in is the patient-reported outcome measure that if the SMA-HI really did allow us to capture this. At present, if we're looking for measures of stamina, those might be the best ones that would indicate an effect.
Great. Thanks. That's exactly what I was looking for.
Thank you, Vernon.
There are no further questions.
Thank you, operator. Thank you to all of the participants on our teleconference today. Thank you for your continued support and interest in Cytokinetics. These data with reldesemtiv in patients with SMA represent for us a dawn of a new day in light of some of the disappointments, admittedly, regarding tirasemtiv and its tolerability profile. Certainly, these data suggest that reldesemtiv, consistent with the therapeutic hypothesis, may be more well-tolerated than tirasemtiv, not only in this population, but in others. Certainly, with these data underscoring increases in time to muscle fatigue as measured by six-minute walk distance, a measure that we think has applicability to not only this population, but potentially others. These are encouraging data around which we hope to be able to now provide further support for this program moving forward.
That together with our partners at Astellas and after further discussions with the SMA community and with regulatory authorities. We thank everybody for their interest and attention this morning. With that operator, we can now conclude the call.
This concludes today's conference call. You may now disconnect.